In recent years, considerable effort has been expended in an attempt to develop new therapeutic agents for the treatment of angina pectoris and associated symptomatology representative of cardiovascular disease. Of such agents, the calcium channel blockers have met with widespread acceptance. Calcium channel antagonists (as they are alternatively referred to) possess diverse chemical structures. These agents possess the ability to block the influx of extracellular calcium during cardiac and vascular smooth muscle depolarization thus leading to a decrease in cytosolic calcium concentration and the concomitant physiological manifestations. Calcium channel agonists are potentially useful in the treatment of heart failure.
Research into the design and synthesis of new chemical entities which can block the calcium channel has progressed largely based on drug screening studies per se in both smooth and cardiac muscle. Such studies have led to speculation concerning the existence of endogenous substances which modulate the activity of the calcium channel and which have therapeutic and diagnostic implications which will be discussed in detail below.